spinocerebellar ataxia 27B, late-onset

Summary

spinocerebellar ataxia 27B, late-onset (MONDO:0859340) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia 27B, late-onset
Mondo ID	MONDO:0859340
OMIM	620174
Orphanet	675216
DOID	DOID:0061137
UMLS	C5774278
MedGen	1824051
GARD	0026707
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant cerebellar ataxia › spinocerebellar ataxia 27B, late-onset

Related subtypes (15): GRID2-related autosomal dominant spinocerebellar ataxia, spinocerebellar ataxia 27A, spinocerebellar ataxia 9, spinocerebellar ataxia 43, spinocerebellar ataxia 7, autosomal dominant cerebellar ataxia type I, autosomal dominant cerebellar ataxia type III, autosomal dominant cerebellar ataxia type IV, spinocerebellar ataxia 49, spinocerebellar ataxia 48, spinocerebellar ataxia 44, spinocerebellar ataxia 47, spinocerebellar ataxia 50, spinocerebellar ataxia 51, spinocerebellar ataxia 52

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 benign/likely benign, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1806479	NG_008317.3:g.245717TTC[250_?]	FGF14	Pathogenic	no assertion criteria provided
2430157	NM_175929.3(FGF14):c.208+239747CTT[250]	FGF14	Pathogenic	criteria provided, single submitter
4813514	NM_004115.4(FGF14):c.353G>T (p.Gly118Val)	FGF14	Pathogenic	criteria provided, single submitter
4291864	NM_175929.3(FGF14):c.208+180774G>A	FGF14	Uncertain significance	criteria provided, single submitter
310902	NM_004115.4(FGF14):c.124G>T (p.Gly42Cys)	FGF14	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGF14	Orphanet:675216	Spinocerebellar ataxia type 27B
FGF14	Orphanet:98764	Spinocerebellar ataxia type 27A

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGF14	HGNC:3671	ENSG00000102466	Q92915	Fibroblast growth factor 14	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGF14	Fibroblast growth factor 14	Probably involved in nervous system development and function.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGF14	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
middle temporal gyrus	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGF14	200	broad	marker	secondary oocyte, middle temporal gyrus, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGF14	1,675

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FGF14	Q92915	79.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Phase 0 - rapid depolarisation	1	346.1×	0.003	FGF14

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
JNK cascade	1	271.8×	0.012	FGF14
neurogenesis	1	208.1×	0.012	FGF14
cell-cell signaling	1	69.6×	0.024	FGF14
nervous system development	1	45.9×	0.027	FGF14
signal transduction	1	16.1×	0.062	FGF14

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGF14	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
FGF14	16	Binding:16

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FGF14

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FGF14	16	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.